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10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents
10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691808/ https://www.ncbi.nlm.nih.gov/pubmed/31307242 http://dx.doi.org/10.1080/14756366.2019.1639695 |
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author | Morak-Młodawska, Beata Pluta, Krystian Latocha, Małgorzata Jeleń, Małgorzata Kuśmierz, Dariusz Suwińska, Kinga Shkurenko, Aleksander Czuba, Zenon Jurzak, Magdalena |
author_facet | Morak-Młodawska, Beata Pluta, Krystian Latocha, Małgorzata Jeleń, Małgorzata Kuśmierz, Dariusz Suwińska, Kinga Shkurenko, Aleksander Czuba, Zenon Jurzak, Magdalena |
author_sort | Morak-Młodawska, Beata |
collection | PubMed |
description | 10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced (1)H and (13)C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and N, N-diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of H3, TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine). |
format | Online Article Text |
id | pubmed-6691808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-66918082019-08-23 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents Morak-Młodawska, Beata Pluta, Krystian Latocha, Małgorzata Jeleń, Małgorzata Kuśmierz, Dariusz Suwińska, Kinga Shkurenko, Aleksander Czuba, Zenon Jurzak, Magdalena J Enzyme Inhib Med Chem Research Paper 10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced (1)H and (13)C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and N, N-diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of H3, TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine). Taylor & Francis 2019-07-16 /pmc/articles/PMC6691808/ /pubmed/31307242 http://dx.doi.org/10.1080/14756366.2019.1639695 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Morak-Młodawska, Beata Pluta, Krystian Latocha, Małgorzata Jeleń, Małgorzata Kuśmierz, Dariusz Suwińska, Kinga Shkurenko, Aleksander Czuba, Zenon Jurzak, Magdalena 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
title | 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
title_full | 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
title_fullStr | 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
title_full_unstemmed | 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
title_short | 10H-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
title_sort | 10h-1,9-diazaphenothiazine and its 10-derivatives: synthesis, characterisation and biological evaluation as potential anticancer agents |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691808/ https://www.ncbi.nlm.nih.gov/pubmed/31307242 http://dx.doi.org/10.1080/14756366.2019.1639695 |
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